Related Experiment Video

Updated: Apr 15, 2026

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.7K

Pleuromutilins Suppress Hepatocellular Carcinoma Growth via ABCA1 Inhibition-Induced Cholesterol Accumulation

Mingshan Zhou1, Jie Cao2, Junfei Chen1,3

  • 1State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

Cancers
|April 14, 2026
PubMed

Insights

Pleuromutilin antibiotics lefamulin and tiamulin show promise for treating hepatocellular carcinoma (HCC). These drugs inhibit tumor growth and enhance anti-tumor immunity by affecting cholesterol transport and increasing CD8+ T-cell infiltration.

Area of Science:

  • Oncology
  • Pharmacology
  • Immunology

Background:

  • Hepatocellular carcinoma (HCC) presents limited therapeutic options, necessitating novel treatment strategies.
  • Drug repurposing, specifically using antibiotics like pleuromutilins, offers a viable approach for anticancer drug discovery.
  • The anticancer potential of lefamulin and tiamulin in HCC remains largely unexplored.

Purpose of the Study:

  • To evaluate the efficacy and safety of lefamulin and tiamulin as potential treatments for hepatocellular carcinoma (HCC).
  • To elucidate the underlying mechanisms of action for lefamulin and tiamulin in HCC, including their effects on cholesterol metabolism and the tumor immune microenvironment.

Main Methods:

  • In vitro and in vivo studies using HCC cell lines, patient-derived organoids, and mouse models.
  • Assessment of drug safety in normal hepatocytes and through histopathological examination of major organs.
  • Mechanistic investigations involving RNA-sequencing, RT-qPCR, immunohistochemistry, filipin staining, and gene silencing.

Main Results:

  • Lefamulin and tiamulin significantly inhibited HCC cell proliferation and suppressed tumor growth in vivo with minimal toxicity.
  • Treatment led to downregulation of the cholesterol transporter ABCA1, causing intracellular cholesterol accumulation.
  • Enhanced CD8+ T-cell infiltration was observed in tumors, suggesting modulation of the tumor immune microenvironment.

Conclusions:

  • Lefamulin and tiamulin demonstrate significant anti-tumor effects in hepatocellular carcinoma models.
  • These pleuromutilin antibiotics represent promising therapeutic candidates for HCC treatment.
  • The observed effects on cholesterol transport and T-cell infiltration provide insights into their anticancer mechanisms.
Keywords:
ABCA1cholesterol metabolismhepatocellular carcinomalefamulintiamulintumor immunity

More Related Videos

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis06:38

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

9.7K
Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype14:51

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Published on: June 17, 2022

3.7K

Related Concept Videos

Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
6.4K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
78
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
70